PROJECT SUMMARY/ABSTRACT Normal physiological aging is associated with a gradual decline in cognitive function across the lifespan, which is exacerbated by the prevalence of mild cognitive impairment (MCI) in the elderly and its progression to Alzheimer?s disease (AD). The overall objective of this project is to identify neural substrates degenerated in aging and MCI and that result in cognitive impairment, and to establish these substrates as targets for rehabilitative strategies aimed are arresting or reversing cognitive decline. Viscoelastic properties of the human brain measured in vivo with magnetic resonance elastography (MRE) have shown to be sensitive to the structure, function, and health of tissue. In particular, MRE has shown that the brain softens in neurodegenerative conditions and that viscoelastic properties of specific structures reflect associated cognitive function in healthy adults; however, the links between viscoelasticity and cognition have yet to be established in populations experiencing decline in cognitive function, such as in aging and MCI. This project seeks to characterize the mechanical integrity of specific memory system structures (i.e. the hippocampus, prefrontal cortex, and associated white matter tracts) through their viscoelastic properties in a geriatric population. We will (1) determine how mechanical integrity of brain tissue is degraded in aging and MCI; (2) determine the relationships between mechanical integrity and memory performance; and (3) determine how the mechanical integrity and associated function is related to fitness level and can be recovered through exercise training. At the end of the project, we will have established brain viscoelasticity as a neural substrate critical for memory function and impairment in a geriatric population and as a target for rehabilitation aimed at improving cognitive function and reducing the burden of disease.